Salivary microRNAs May Be A Valuable Biomarker To Detect Resectable Pancreatic Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Xie Zijun
PROVIDER: S-ECPF-GEOD-53325 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Early surgery is vital in the treatment of highly fatal pancreatic cancer (PC). But there is no valuable and non-invasive biomarker to screen PC currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary microRNAs (miRNAs) can act as a biomarker to detect resectable PC.
2013-12-15 | GSE53325 | GEO
Project description:Early surgery is vital in the treatment of highly fatal pancreatic cancer (PC). But there is no valuable and non-invasive biomarker to screen PC currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary microRNAs (miRNAs) can act as a biomarker to detect resectable PC. By Agilent microarray salivary miRNAs were profiled from saliva samples from 8 patients with resectable PC and 8 healthy controls. Candidate biomarkers discovered from the profile were subjected to validation by qPCR.
2013-12-15 | E-GEOD-53325 | biostudies-arrayexpress
Project description:Lack of detection technology for early pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. New strategies and biomarkers for early detection are sorely needed. In this study, we have conducted a prospective sample collection and retrospective blinded validation to evaluate the performance and translational utilities of salivary transcriptomic biomarkers for the noninvasive detection of resectable pancreatic cancer.The Affymetrix HG U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) was used to profile transcriptomes and discover altered gene expression in saliva supernatant. Biomarkers discovered from the microarray study were subjected to clinical validation using an independent sample set of 30 pancreatic cancer patients, 30 chronic pancreatitis patients, and 30 healthy controls.Twelve messenger RNA biomarkers were discovered and validated. The logistic regression model with the combination of 4 messenger RNA biomarkers (KRAS, MBD3L2, ACRV1, and DPM1) could differentiate pancreatic cancer patients from noncancer subjects (chronic pancreatitis and healthy control), yielding a receiver operating characteristic plot, area under the curve value of 0.971 with 90.0% sensitivity and 95.0% specificity.The salivary biomarkers possess discriminatory power for the detection of resectable pancreatic cancer, with high specificity and sensitivity. This report provides the proof of concept of salivary biomarkers for the noninvasive detection of a systemic cancer and paves the way for prediction model validation study followed by pivotal clinical validation.
| S-EPMC2831159 | biostudies-literature
Project description:Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer, and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of the biological and mechanistic rationale as to why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Panc02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineering a Panc02 cell line that is suppressed for exosome biogenesis, implanting into the C56BL/6 mouse, and examining whether the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases.
| S-EPMC3772238 | biostudies-literature
Project description:BackgroundBlood-based biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Current biomarkers lack high sensitivity and specificity for population screening. The gold-standard biomarker, CA 19-9, also fails to demonstrate the predictive value necessary for early detection.MethodsTo validate a functional genomics-based plasma migration signature biomarker panel, plasma tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FN III-C), and CA 19-9 levels were measured by enzyme-linked immunosorbent assays in three early-stage PDAC plasma cohorts, including two independent blinded validation cohorts containing a total of 43 stage I, 163 stage II, 86 chronic pancreatitis, 31 acute biliary obstruction, and 108 controls. Logistic regression models developed classification rules combining TFPI and/or TNC-FN III-C with CA 19-9 for patient cases and control subjects, with or without adjustment for age and diabetes status. Model classification performance was evaluated and analyses repeated among subpopulations without diabetes and pancreatitis history. Two-sided P values were calculated using bootstrap method.ResultsThe TFPI/TNC-FN III-C/CA 19-9 panel improved CA 19-9 performance in all early-stage cohorts, including discriminating stage IA/IB/IIA, stage IIB, and all early-stage cancer from healthy controls. Statistical significance was reached for a number of subcohorts, including for all early-stage cancer vs healthy controls (cohort 1 AUC = 0.92, 95% CI = 0.86 to 0.96, P = .04; cohort 3 AUC = 0.83, 95% CI = 0.76 to 0.89, P = .045). Among subcohorts without diabetes and pancreatitis history, the panel approaches potential clinical utility for early detection to discriminate early-stage PDAC from healthy controls including an area under the curve (AUC) of 0.87 (95% CI = 0.77 to 0.95) for stage I/IIA, an AUC of 0.93 (95% CI = 0.87 to 0.98) for stage IIB, and a statistically significant AUC of 0.89 (95% CI = 0.82 to 0.95) for all early-stage cancer ( P = .03).ConclusionsTFPI/TNC-FN III-C migration signature adds statistically significantly to CA 19-9's predictive power to detect early-stage PDAC and may have clinical utility for early detection of surgically resectable PDAC, as well as for enhanced survival from this routinely lethal cancer.
| S-EPMC6059209 | biostudies-literature
Project description:Pancreatic cancer is one of the most malignant cancer types and has a poor prognosis. It is often diagnosed at an advanced stage because of the absence of typical symptoms. Therefore, it is necessary to establish a screening method for the early detection of pancreatic cancer in high-risk individuals. This is a prospective validation study conducted in a cohort of 1033 Japanese individuals (male, n = 467, age = 63.3 ± 11.5 years; female, n = 566, age = 64.2 ± 10.6 years) to evaluate the use of salivary polyamines for screening pancreatic diseases and cancers. Patients with pancreatic cancer were not included; however, other pancreatic diseases were treated as positive cases for accuracy verification. Of the 135 individuals with elevated salivary polyamine markers, 66 had pancreatic diseases, such as chronic pancreatitis and pancreatic cysts, and 1 had gallbladder cancer. These results suggest that the salivary polyamine panel is a useful noninvasive pancreatic disease screening tool.
| S-EPMC9918012 | biostudies-literature
Project description:The use of neoadjuvant therapies has played a major role for borderline resectable and locally advanced pancreatic cancers (PCs). For this group of patients, preoperative chemotherapy or chemoradiation has increased the likelihood of surgery with negative resection margins and overall survival. On the other hand, for patients with resectable PC, the main rationale for neoadjuvant therapy is that the overall survival with current strategies is unsatisfactory. There is a consensus that we need new treatments to improve the overall survival and quality of life of patients with PC. However, without strong scientific evidence supporting the theoretical advantages of neoadjuvant therapies, these potential benefits might turn out not to be worth the risk of tumors progression while waiting for surgery. The focus of this paper is to provide the readers an overview of the most recent evidence on this subject.
| S-EPMC5740086 | biostudies-literature
Project description:Approximately 20% of pancreatic ductal adenocarcinoma (PDAC) patients have (borderline) resectable pancreatic cancer [(B)RPC] at diagnosis. Upfront resection with adjuvant chemotherapy has long been the standard of care for these patients. However, although surgical quality has improved, still about 50% of patients never receive adjuvant treatment. Therefore, recent developments have focused on a neoadjuvant approach. Directly comparing results from neoadjuvant and adjuvant regimens is challenging due to differences in patient populations that influence outcomes. Neoadjuvant trials include all patients who have (B)RPC on imaging, while adjuvant-only trials include patients who underwent a complete resection and recovered to a good performance status without any evidence of residual disease. Guidelines recommend neoadjuvant treatment for BRPC patients mainly to improve negative resection margin (R0) rates. For resectable PDAC, upfront resection is still considered the standard of care. However, theoretical advantages of neoadjuvant treatment, including the increased R0 resection rate, early delivery of systemic therapy to all patients, directly addressing occult metastatic disease, and improved patient selection for resection, may also apply to these patients. A systematic review by intention-to-treat showed a superior median overall survival (OS) for any neoadjuvant approach (19 months) compared to upfront surgery (15 months) in (B)RPC patients. A neoadjuvant approach was recently supported by three randomized controlled trials (RCTs). For resectable PDAC, neoadjuvant treatment was superior in a Japanese RCT of neoadjuvant gemcitabine with S-1 vs. upfront surgery, with adjuvant S-1 in both arms (median OS: 37 vs. 27 months, p = 0.015). A Korean trial of neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront resection in BRPC patients was terminated early due to superiority of the neoadjuvant group (median OS: 21 vs. 12 months, p = 0.028; R0 resection: 52 vs. 26%, p = 0.004). The PREOPANC-1 trial for (B)RPC patients also showed favorable outcome for neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront surgery (median OS: 17 vs. 14 months, p = 0.07; R0 resection: 63 vs. 31%, p < 0.001). FOLFIRINOX is likely a better neoadjuvant regimen, because of superiority compared to gemcitabine in both the metastatic and adjuvant setting. Currently, five RCTs evaluating neoadjuvant modified or fulldose FOLFIRINOX are accruing patients.
| S-EPMC7005204 | biostudies-literature
Project description:PurposeNeoadjuvant chemoradiation is an alternative to the surgery-first approach for resectable pancreatic cancer (PDA) and represents the standard of care for borderline resectable (BLR).Materials and methodsAll patients with resectable and BLR PDA treated with neoadjuvant chemoradiation using IMRT between 1/2009 and 11/2011 were reviewed. Patients were treated to a customized CTV which included the primary mass and regional vessels.ResultsNeoadjuvant chemoradiation was completed in 69 patients (39 BLR and 30 resectable). Induction chemotherapy was used in 32 (82%) of the 39 patients with BLR disease prior to chemoXRT. All resectable patients were treated with chemoXRT alone. Following neoadjuvant treatment, 48 (70%) of the 69 patients underwent successful pancreatic resection with 47 (98%) being margin negative (RO). In 30 of the BLR patients who had arterial abutment or SMV occlusion, 19 (63%) were surgically resected and all had RO resections. The cumulative incidence of local failure at 1 and 2 years was 2% (95% CI 0-6%) and 9% (95% CI 0.6-17%) respectively. The median overall survival for all patients, patients undergoing resection, and patients without resection were 20, 26 and 11 months respectively. Sixteen (23%) of the 69 patients are alive without disease with a median follow-up of 47 months (36-60).ConclusionNeoadjuvant chemoXRT can facilitate a margin negative resection in patients with localized PCa.
| S-EPMC4530020 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Curative-intended resection and adjuvant chemotherapy represents the current standard of care. Despite substantial improvements in surgical treatment and intensified adjuvant treatment with more powerful regimens over the last years even clearly resectable pancreatic cancer still has an unfavorable prognosis with a high risk of relapse. Neoadjuvant or perioperative multimodal therapies have substantially improved the outcome of other resectable gastrointestinal (GI) cancers such as esophagus and gastric cancer. It is reasonable to assume that efficient chemotherapy and or radiochemotherapy may have a similar impact on the outcome of resectable PDAC. This review is focused on neoadjuvant and perioperative treatment of resectable PDAC (no borderline resectable or locally advanced PDAC), summarizes the pros and cons for neoadjuvant treatment in the context of the current literature, and also provides an overview over the landscape of ongoing clinical trials in this up-and-coming field of PDAC therapy.
| S-EPMC6458347 | biostudies-literature